This study investigated the replacement of soybean meal by cottonseed meal in diets for the Chinese mitten crab, Eriocheir sinensis. Seven isocaloric and isonitrogenous diets were tested with five replicates of each treatment. Cottonseed meal replaced 33%, 66%, or 100% of the soybean meal in three diets, while lysine was added to another three containing the same amounts of cottonseed meal. The control contained neither cottonseed meal nor lysine. Protein digestibility decreased with the increase of dietary cottonseed mealand was significantly lower in the 100% treatment than in the control. Dry matter in the body of crabs fed the 33%, 66%, 100%, and 33%+lysine diets was significantly lower than that of the control. Whole body protein decreased as the cottonseed meal content increased, and was significantly lower in crabs fed the 100% diet than in control crabs. Crabs fed the control diet contained higher lipid than those fed other diets, while crabs fed diets containing lysine had significantly lower lipid than crabs fed the 33% diet. Crabs fed the 100%+lysine diet had a significantly higher ash content than those fed the 33% or 100% diets. In conclusion, this study indicates that 66% of soybean meal can be replaced by cottonseed meal in crab diets and 100% of soybean meal can be replaced by cottonseed meal when supplemented by lysine.